Genetic Variant NM_002828.4:c.700G>T (chr18-12817161-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_002828.4(PTPN2):c.700G>T(p.Val234Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V234I) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Consequence

PTPN2
NM_002828.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.961

Publications

0 publications found

Variant links:

Genes affected

PTPN2 (HGNC:9650): (protein tyrosine phosphatase non-receptor type 2) The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. Members of the PTP family share a highly conserved catalytic motif, which is essential for the catalytic activity. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. Epidermal growth factor receptor and the adaptor protein Shc were reported to be substrates of this PTP, which suggested the roles in growth factor mediated cell signaling. Multiple alternatively spliced transcript variants encoding different isoforms have been found. Two highly related but distinctly processed pseudogenes that localize to chromosomes 1 and 13, respectively, have been reported. [provided by RefSeq, May 2011]

PTPN2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3530724).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002828.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PTPN2	NM_002828.4	MANE Select	c.700G>T	p.Val234Phe	missense	Exon 6 of 9	NP_002819.2	P17706-1
PTPN2	NM_001207013.2		c.769G>T	p.Val257Phe	missense	Exon 7 of 11	NP_001193942.1	P17706-4
PTPN2	NM_080422.3		c.700G>T	p.Val234Phe	missense	Exon 6 of 10	NP_536347.1	P17706-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PTPN2	ENST00000309660.10	TSL:1 MANE Select	c.700G>T	p.Val234Phe	missense	Exon 6 of 9	ENSP00000311857.3	P17706-1
PTPN2	ENST00000591115.5	TSL:1	c.769G>T	p.Val257Phe	missense	Exon 7 of 11	ENSP00000466936.1	P17706-4
PTPN2	ENST00000327283.7	TSL:1	c.700G>T	p.Val234Phe	missense	Exon 6 of 10	ENSP00000320298.3	P17706-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

-0.020

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.54

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.31

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.84

M_CAP

Benign

0.059

MetaRNN

Benign

0.35

MetaSVM

Benign

-0.37

MutationAssessor

Benign

2.0

PhyloP100

0.96

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-4.0

REVEL

Uncertain

0.54

Sift

Uncertain

0.0080

Sift4G

Pathogenic

0.0010

Polyphen

0.066

Vest4

0.59

MutPred

0.47

Loss of ubiquitination at K238 (P = 0.1079)

MVP

0.94

MPC

0.14

ClinPred

0.95

GERP RS

2.3

Varity_R

0.38

gMVP

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over